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The natural vulnerability to the climate change phenomenon due to the unique topographic and climatic conditions in the Middle East adds significance to an already important issue of evaluating the simulations of general circulation models (GCMs) in this region. To this end, this study employed time series analysis to evaluate GCMs' simulations, in terms of the air temperature variable, with regard to the observed climatic behaviors of Karkheh River basin, Iran. Resultantly, each of the GCMs' time series was broken down into three principal components (i.e., periodicity, trend, and stochastic component), and each component was analyzed accordingly. Results demonstrated that the simulations from different models significantly differed. Even though some models like CSIR-MK3.5 and INGV-SXG outperformed others in representing an accurate estimation of the historical climatic behavior of the southern plains of the Karkheh River, the GCMs could not provide a realistic simulation of the historical climatic behavior for the topographically challenging areas, like the northern mountainous parts of the basin. It should be noted that while the results from such analyses would shed light on the variability of the GCMs' simulations in regional-scale studies, the results, under no circumstances, provide evidence indicating that one model is more accurate than another.